Many observation studies have demonstrated a close relationship between rheumatoid arthritis (RA) and osteoporosis (OP). However, the causal genetic correlation between RA and OP remains unclear. In this study, we performed bi-directional Mendelian randomization (MR) analyses to explore causal inference between these two traits. The instrumental variables for RA were selected from a large-scale genome-wide association study (GWAS) (1,523 cases and 461,487 controls). Bone mineral density (BMD) at five different sites (heel (n=265,627), forearm (FA) (n=8,143), femoral neck (FN) (n=32,735), lumbar spine (LS) (n=28,498), and total body (n=28,498)) were used as phenotypes for OP. The inverse variance weighted (IVW) method did not detect any causal effect of BMDs on RA except heel BMD (beta = -7.57 × 10-4, p = 0.02). However, other methods (MR-Egger, weighted median, weighted mode, MR-PRESSO, and MR-RAPS) showed no causal association between heel BMD and RA. Likewise, we did not find a causal effect of RA on BMD at any sites. In conclusion, we found no evidence that RA is causally associated with OP/BMD, or vice versa. We suggested that the associations found in previous observational studies between RA and OP/BMD are possibly related to secondary effects such as antirheumatic treatment and reduced physical activity.Laryngeal squamous cell carcinoma (LSCC) is a common head and neck cancer with a high metastasis and poor prognosis. Circular RNAs (circRNAs) are a type of non-coding RNAs (ncRNAs) with regulatory function and broadly participate in cancer development. However, the correlation of circular RNA ABCB10 (circABCB10) with LSCC remains unclear. Here, we were interested in the role of circABCB10 in the modulation of LSCC progression. Our data demonstrated that the depletion of circABCB10 significantly inhibited the proliferation and induced the apoptosis of LSCC cells. Meanwhile, circABCB10 knockdown was able to remarkably reduce the invasion and migration of LSCC cells. Mechanically, circABCB10 served as a sponge for microRNAs-588 (miR-588) and miR-588 could target and down-regulated chemokine receptor 4 (CXCR4) expression in LSCC cells. The overexpression of CXCR4 or miR-588 inhibitor could reverse circABCB10 depletion-attenuated malignant phenotypes of LSCC cells. Functionally, the depletion of circABCB10 alleviated the tumor growth of LSCC cells in the tumorigenicity analysis of nude mice. The CXCR4 expression was decreased while the miR-588 expression was enhanced by circABCB10 depletion in vivo. https://www.selleckchem.com/ Thus, we concluded that circABCB10 was involved in the malignant progression of LSCC by regulating miR-588/CXCR4 axis. Our finding provides new insights into the mechanism of circRHOT1 contributing to the development of LSCC. CircABCB10 and miR-588 may be used as potential targets for the treatment of LSCC.Intervertebral disc degeneration (IDD) is the prevailing spine disorder and is associated with musculoskeletal disease. The extracellular matrix (ECM) degradation is an essential hallmark of IDD progression. Circular RNAs (circRNAs), as crucial cellular regulators, participate in multiple pathological processes including IDD. Here, we tried to explore the effect of circITCH on the ECM degradation of IDD and the underlying mechanism. Significantly, the expression levels of circITCH were elevated in the IDD patients' nucleus pulposus (NP) tissues relative to that of normal cases. CircITCH promoted apoptosis and decreased proliferation of NP cells. CircITCH contributed to ECM degradation, as demonstrated by increased ADAMTS4 and MMP13 expression and decreased aggrecan and collagen II expression. Mechanically, miR-17-5p could be sponged by circITCH and miR-17-5p inhibited ECM degradation by repressing SOX4 in degenerative NP cells. CircITCH could activate Wnt/β-catenin pathway by targeting miR-17-5p/SOX4 signaling. SOX4 overexpression, miR-17-5p inhibitor, or Wnt/β-catenin signaling activator LiCl was able to reverse circITCH knockdown-inhibited apoptosis and ECM degradation, and circITCH knockdown-enhanced proliferation in NP cells. Thus, we conclude that circITCH promotes ECM degradation in IDD by activating Wnt/β-catenin through miR-17-5p/SOX4 signaling. Our finding presents novel insight into the mechanism that circITCH modulates the IDD progression. CircITCH and SOX4 may serve as potential targets for IDD therapy.Osteosarcoma is a malignant tumor with high mortality in children and adolescents. The mechanism of osteosarcoma metastasis is currently unclear. Abnormal expression of long non-coding RNA (lncRNA) plays an important role in tumor metastasis. We used bioinformatics to analyze the differences in gene expression between osteosarcoma in situ and osteosarcoma lung metastases. CCK-8 was used to detect the effect of lncRNA LOC100129620 on the proliferation of osteosarcoma cells. The effect of LOC100129620 on the invasion of osteosarcoma cells was assessed by Transwell assay. The regulatory effect of LOC100129620 on miR-335-3p was examined using RNA pull-down and luciferase reporter gene assays. The effect of LOC100129620 on the polarization of macrophages was detected by quantitative real-time fluorescent PCR. The results show that LOC100129620 can promote the proliferation and migration of osteosarcoma cells. LOC100129620 can promote the proliferation of osteosarcoma in vivo. LOC100129620 can bind to miR-335-3p and regulate its function. MiR-335-3p mediates the regulatory effects of LOC100129620 on CDK6. LOC100129620 promotes the formation of blood vessels and the polarization of macrophages. The LOC100129620/miR-335-3p/CDK6 signaling pathway promotes the metastasis of osteosarcoma by regulating the proliferation of osteosarcoma cells, angiogenesis, and macrophage polarization.Metabolic reprogramming is emerging as a key pathological contributor to the progression of autosomal dominant polycystic kidney disease (ADPKD), but the molecular mechanisms underlying dysregulated cellular metabolism remain elusive. Here we report that amino acid biosynthesis is reprogrammed in Pkd2-knockout mouse kidneys via a defective PERK-eIF2?-ATF4 pathway. Transcriptomic analysis revealed that the amino acid biosynthesis pathways such as serine, arginine and cysteine were impaired, and associated critical enzymes were downregulated in Pkd2-knockout mouse kidneys. ATF4 and CHOP, transcription factors downstream of the endoplasmic reticulum (ER) stress sensor PERK, were identified as master regulators of these enzymes' expression. PKD2 deficiency impaired the expression of ATF4 and amino acid synthesis enzymes in RCTEC cells under ER stress. Mechanistically, as an ER-resident protein, PKD2 interacts with TBL2, which functions as an adaptor bridging eIF2? to PERK. PKD2 depletion impaired the recruitment of eIF2? to TBL2, thus impeding activation of the PERK-eIF2?-ATF4 pathway and downstream amino acid biosynthesis.